Natural selection in avian protein-coding genes expressed in brain

The evolution of birds from theropod dinosaurs took place approximately 150 million years ago, and was associated with a number of specific adaptations that are still evident among extant birds, including feathers, song and extravagant secondary sexual characteristics. Knowledge about the molecular evolutionary background to such adaptations is lacking. Here, we analyse the evolution of > 5000 protein-coding gene sequences expressed in zebra finch brain by comparison to orthologous sequences in chicken. Mean d _N/ d _S is 0.085 and genes with their maximal expression in the eye and central nervous system have the lowest mean d _N/ d _S value, while those expressed in digestive and reproductive tissues exhibit the highest. We find that fast-evolving genes (those which have higher than expected rate of nonsynonymous substitution, indicative of adaptive evolution) are enriched for biological functions such as fertilization, muscle contraction, defence response, response to stress, wounding and endogenous stimulus, and cell death. After alignment to mammalian orthologues, we identify a catalogue of 228 genes that show a significantly higher rate of protein evolution in the two bird lineages than in mammals. These accelerated bird genes, representing candidates for avian-specific adaptations, include genes implicated in vocal learning and other cognitive processes. Moreover, colouration genes evolve faster in birds than in mammals, which may have been driven by sexual selection for extravagant plumage characteristics.     

Condition‐dependent mutation rates and sexual selection

‘Good genes’ models of sexual selection show that females can gain indirect benefits for their offspring if male ornaments are condition‐dependent signals of genetic quality. Recurrent deleterious mutation is viewed as a major contributor to variance in genetic quality, and previous theoretical treatments of ‘good genes’ processes have assumed that the influx of new mutations is constant. I propose that this assumption is too simplistic, and that mutation rates vary in ways that are important for sexual selection. Recent data have shown that individuals in poor condition can have higher mutation rates, and I argue that if both male sexual ornaments and mutation rates are condition‐dependent, then females can use male ornamentation to evaluate their mate’s mutation rate. As most mutations are deleterious, females benefit from choosing well‐ornamented mates, as they are less likely to contribute germline‐derived mutations to offspring. I discuss some of the evolutionary ramifications of condition‐dependent mutation rates and sexual selection.     

Genic mutation rates in mammals: local similarity,chromosomal heterogeneity,and X-versus-autosome disparity

The reduction of mutation rates on the mammalian X chromosome relative to autosomes is most often explained in the literature as evidence of male-driven evolution. This hypothesis attributes lowered mutation rates on the X chromosome to the fact that this chromosome spends less time in the germline of males than in the germline of females. In contrast to this majority view, two articles argued that the patterns of mutation rates across chromosomes are inconsistent with male-driven evolution. One article reported a 40% reduction in synonymous substitution rates (Ks) for X-linked genes relative to autosomes in the mouse-rat lineage. The authors argued that this reduction is too dramatic to be explained by male-driven evolution and concluded that selection has systematically reduced mutation rate on the X chromosome to a level optimal for this male-hemizygous chromosome. More recently, a second article found that chromosomal mutation rates in both the human-mouse and mouse-rat lineages were so heterogeneous that the X chromosome was not an outlier. Here again, the authors argued that this is at odds with male-driven evolution and suggested that selection has modulated chromosomal mutation rates to locally optimal levels, thus extending the argument of the first mentioned article to include autosomes. Here, we reexamine these conclusions using mouse-rat and human-mouse coding-region data. We find a more modest reduction of Ks on the X chromosome, but our results contradict the finding that the X chromosome is not distinct from autosomes. Multiple statistical tests show that Ks rates on the X chromosome differ systematically from the autosomes in both lineages. We conclude that the moderate reduction of mutation rate on the X chromosome of both lineages is consistent with male-driven evolution; however, the large variance in mutation rates across chromosomes suggests that mutation rates are affected by additional factors besides male-driven evolution. Investigation of mutation rates by synteny reveals that synteny blocks, rather than entire chromosomes, might represent the unit of mutation rate variation.     

Higher rates of sex evolve under K‐selection

The geographical distribution of sexual and related asexual species has been suggested to correlate with habitat stability; sexual species tend to be in stable habitats (K‐selection), whereas related asexual taxa tend to be in unstable habitats (r‐selection). We test whether this broad‐scale pattern can be re‐created at a microevolutionary scale by experimentally evolving populations of facultatively sexual rotifers under different ecological conditions. Consistent with the pattern in nature, we find that the rate of sex evolves to lower levels in the r‐selected than in K‐selection environments. We consider several different explanations for these results.     

The evolution of bacterial mutation rates under simultaneous selection by interspecific and social parasitism

Many bacterial populations harbour substantial numbers of hypermutable bacteria, in spite of hypermutation being associated with deleterious mutations. One reason for the persistence of hypermutators is the provision of novel mutations, enabling rapid adaptation to continually changing environments, for example coevolving virulent parasites. However, hypermutation also increases the rate at which intraspecific parasites (social cheats) are generated. Interspecific and intraspecific parasitism are therefore likely to impose conflicting selection pressure on mutation rate. Here, we combine theory and experiments to investigate how simultaneous selection from inter- and intraspecific parasitism affects the evolution of bacterial mutation rates in the plant-colonizing bacterium Pseudomonas fluorescens. Both our theoretical and experimental results suggest that phage presence increases and selection for public goods cooperation (the production of iron-scavenging siderophores) decreases selection for mutator bacteria. Moreover, phages imposed a much greater growth cost than social cheating, and when both selection pressures were imposed simultaneously, selection for cooperation did not affect mutation rate evolution. Given the ubiquity of infectious phages in the natural environment and clinical infections, our results suggest that phages are likely to be more important than social interactions in determining mutation rate evolution.     

Clonal Interference in the Evolution of Influenza

The seasonal influenza A virus undergoes rapid evolution to escape human immune response. Adaptive changes occur primarily in antigenic epitopes, the antibody-binding domains of the viral hemagglutinin. This process involves recurrent selective sweeps, in which clusters of simultaneous nucleotide fixations in the hemagglutinin coding sequence are observed about every 4 years. Here, we show that influenza A (H3N2) evolves by strong clonal interference. This mode of evolution is a red queen race between viral strains with different beneficial mutations. Clonal interference explains and quantifies the observed sweep pattern: we find an average of at least one strongly beneficial amino acid substitution per year, and a given selective sweep has three to four driving mutations on average. The inference of selection and clonal interference is based on frequency time series of single-nucleotide polymorphisms, which are obtained from a sample of influenza genome sequences over 39 years. Our results imply that mode and speed of influenza evolution are governed not only by positive selection within, but also by background selection outside antigenic epitopes: immune adaptation and conservation of other viral functions interfere with each other. Hence, adapting viral proteins are predicted to be particularly brittle. We conclude that a quantitative understanding of influenza’s evolutionary and epidemiological dynamics must be based on all genomic domains and functions coupled by clonal interference.     

Elevated rates of positive selection drive the evolution of pestiferousness in the Colorado potato beetle (Leptinotarsa decemlineata,Say)

Contextualizing evolutionary history and identifying genomic features of an insect that might contribute to its pest status is important in developing early detection and control tactics. In order to understand the evolution of pestiferousness, which we define as the accumulation of traits that contribute to an insect population's success in an agroecosystem, we tested the importance of known genomic properties associated with rapid adaptation in the Colorado potato beetle (CPB), Leptinotarsa decemlineata Say. Within the leaf beetle genus Leptinotarsa, only CPB, and a few populations therein, has risen to pest status on cultivated nightshades, Solanum. Using whole genomes from ten closely related Leptinotarsa species native to the United States, we reconstructed a high‐quality species tree and used this phylogenetic framework to assess evolutionary patterns in four genomic features of rapid adaptation: standing genetic variation, gene family expansion and contraction, transposable element abundance and location, and positive selection at protein‐coding genes. Throughout approximately 20 million years of history, Leptinotarsa species show little evidence of gene family turnover and transposable element variation. However, there is a clear pattern of CPB experiencing higher rates of positive selection on protein‐coding genes. We determine that these rates are associated with greater standing genetic variation due to larger effective population size, which supports the theory that the demographic history contributes to rates of protein evolution. Furthermore, we identify a suite of coding genes under positive selection that are putatively associated with pestiferousness in the Colorado potato beetle lineage. They are involved in the biological processes of xenobiotic detoxification, chemosensation and hormone function.     

Comparative genomics reveals high rates of horizontal transfer and strong purifying selection on rhizobial symbiosis genes

Horizontal transfer (HT) alters the repertoire of symbiosis genes in rhizobial genomes and may play an important role in the on-going evolution of the rhizobia–legume symbiosis. To gain insight into the extent of HT of symbiosis genes with different functional roles (nodulation, N-fixation, host benefit and rhizobial fitness), we conducted comparative genomic and selection analyses of the full-genome sequences from 27 rhizobial genomes. We find that symbiosis genes experience high rates of HT among rhizobial lineages but also bear signatures of purifying selection (low Ka : Ks). HT and purifying selection appear to be particularly strong in genes involved in initiating the symbiosis (e.g. nodulation) and in genome-wide association candidates for mediating benefits provided to the host. These patterns are consistent with rhizobia adapting to the host environment through the loss and gain of symbiosis genes, but not with host-imposed positive selection driving divergence of symbiosis genes through recurring bouts of positive selection.     

Shifts in the evolutionary rate and intensity of purifying selection between two Brassica genomes revealed by analyses of orthologous transposons and relics of a whole genome triplication

Recent sequencing of the Brassica rapa and Brassica oleracea genomes revealed extremely contrasting genomic features such as the abundance and distribution of transposable elements between the two genomes. However, whether and how these structural differentiations may have influenced the evolutionary rates of the two genomes since their split from a common ancestor are unknown. Here, we investigated and compared the rates of nucleotide substitution between two long terminal repeats (LTRs) of individual orthologous LTR‐retrotransposons, the rates of synonymous and non‐synonymous substitution among triplicated genes retained in both genomes from a shared whole genome triplication event, and the rates of genetic recombination estimated/deduced by the comparison of physical and genetic distances along chromosomes and ratios of solo LTRs to intact elements. Overall, LTR sequences and genic sequences showed more rapid nucleotide substitution in B. rapa than in B. oleracea. Synonymous substitution of triplicated genes retained from a shared whole genome triplication was detected at higher rates in B. rapa than in B. oleracea. Interestingly, non‐synonymous substitution was observed at lower rates in the former than in the latter, indicating shifted densities of purifying selection between the two genomes. In addition to evolutionary asymmetry, orthologous genes differentially regulated and/or disrupted by transposable elements between the two genomes were also characterized. Our analyses suggest that local genomic and epigenomic features, such as recombination rates and chromatin dynamics reshaped by independent proliferation of transposable elements and elimination between the two genomes, are perhaps partially the causes and partially the outcomes of the observed inter‐specific asymmetric evolution.     

Temporal patterns of fruit fly (Drosophila) evolution revealed by mutation clocks

Drosophila melanogaster has been a canonical model organism to study genetics, development, behavior, physiology, evolution, and population genetics for nearly a century. Despite this emphasis and the completion of its nuclear genome sequence, the timing of major speciation events leading to the origin of this fruit fly remain elusive because of the paucity of extensive fossil records and biogeographic data. Use of molecular clocks as an alternative has been fraught with non-clock-like accumulation of nucleotide and amino-acid substitutions. Here we present a novel methodology in which genomic mutation distances are used to overcome these limitations and to make use of all available gene sequence data for constructing a fruit fly molecular time scale. Our analysis of 2977 pairwise sequence comparisons from 176 nuclear genes reveals a long-term fruit fly mutation clock ticking at a rate of 11.1 mutations per kilobase pair per Myr. Genomic mutation clock-based timings of the landmark speciation events leading to the evolution of D. melanogaster show that it shared most recent common ancestry 5.4 MYA with D. simulans, 12.6 MYA with D. erecta+D. orena, 12.8 MYA with D. yakuba+D. teisseri, 35.6 MYA with the takahashii subgroup, 41.3 MYA with the montium subgroup, 44.2 MYA with the ananassae subgroup, 54.9 MYA with the obscura group, 62.2 MYA with the willistoni group, and 62.9 MYA with the subgenus Drosophila. These and other estimates are compatible with those known from limited biogeographic and fossil records. The inferred temporal pattern of fruit fly evolution shows correspondence with the cooling patterns of paleoclimate changes and habitat fragmentation in the Cenozoic.     

Rapid evolution of testis size relative to sperm morphology suggests that post‐copulatory selection targets sperm number in Anolis lizards

Post‐copulatory sexual selection is thought to be responsible for much of the extraordinary diversity in sperm morphology across metazoans. However, the extent to which post‐copulatory selection targets sperm morphology versus sperm production is generally unknown. To address this issue, we simultaneously characterized the evolution of sperm morphology (length of the sperm head, midpiece and flagellum) and testis size (a proxy for sperm production) across 26 species of Anolis lizards, a group in which sperm competition is likely. We found that the length of the sperm midpiece has evolved 2–3 times faster than that of the sperm head or flagellum, suggesting that midpiece size may be the most important aspect of sperm morphology with respect to post‐copulatory sexual selection. However, testis size has evolved faster than any aspect of sperm morphology or body size, supporting the hypothesis that post‐copulatory sexual selection acts more strongly upon sperm production than upon sperm morphology. Likewise, evolutionary increases in testis size, which typically indicate increased sperm competition, are not associated with predictable changes in sperm morphology, suggesting that any effects of post‐copulatory selection on sperm morphology are either weak or variable in direction across anoles. Collectively, our results suggest that sperm production is the primary target of post‐copulatory sexual selection in this lineage.     

Natural selection in the <Emphasis Type="Italic">TLR-</Emphasis>related genes in the course of primate evolution

The innate immune system constitutes the front line of host defense against pathogens. Toll-like receptors (TLRs) recognize molecules derived from pathogens and play crucial roles in the innate immune system. Here, we provide evidence that the TLR-related genes have come under natural selection pressure in the course of primate evolution. We compared the nucleotide sequences of 16 TLR-related genes, including TLRs (TLR1–10), MYD88, TILAP, TICAM1, TICAM2, MD2, and CD14, among seven primate species. Analysis of the non-synonymous/synonymous substitution ratio revealed the presence of both strictly conserved and rapidly evolving regions in the TLR-related genes. The genomic segments encoding the intracellular Toll/interleukin 1 receptor domains, which exhibited lower rates of non-synonymous substitution, have undergone purifying selection. In contrast, TLR4, which carried a high proportion of non-synonymous substitutions in the part of extracellular domain spanning 200 amino acids, was found to have been the suggestive target of positive Darwinian selection in primate evolution. However, sequence analyses from 25 primate species, including eight hominoids, six Old World monkeys, eight New World monkeys, and three prosimians, showed no evidence that the pressure of positive Darwinian selection has shaped the pattern of sequence variations in TLR4 among New World monkeys and prosimians. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Sexual selection and maintenance of sex: evidence from comparisons of rates of genomic accumulation of mutations and divergence of sex-related genes in sexual and hermaphroditic species of Caenorhabditis

Several hypotheses have been proposed to explain the persistenceof dioecy despite the reproductive advantages conferred to hermaphrodites,including greater efficiency at purging deleterious mutationsin the former. Dioecy can benefit from both mutation purgingand accelerated evolution by bringing together beneficial mutationsin the same individual via recombination and shuffling of genotypes.In addition, mathematical treatment has shown that sexual selectionis also capable of mitigating the cost of maintaining separatesexes by increasing the overall fitness of sexual populations,and genomic comparisons have shown that sexual selection canlead to accelerated evolution. Here, we examine the advantagesof dioecy versus hermaphroditism by comparing the rate of evolutionin sex-related genes and the rate of accumulation of deleteriousmutations using a large number of orthologs (11,493) in thedioecious Caenorhabditis remanei and the hermaphroditic Caenorhabditisbriggsae. We have used this data set to estimate the deleteriousmutation rate per generation, U, in both species and find thatalthough it is significantly higher in hermaphrodites, bothspecies are at least 2 orders of magnitude lower than the valuerequired to explain the persistence of sex by efficiency atpurging deleterious mutations alone. We also find that genesexpressed in sperm are evolving rapidly in both species; however,they show a greater increase in their rate of evolution relativeto genes expressed in other tissues in C. remanei, suggestingstronger sexual selection pressure acting on these genes indioecious species. Interestingly, the persistence of a signalof rapid evolution of sperm genes in C. briggsae suggests arecent evolutionary origin of hermaphrodism in this lineage.Our results provide empirical evidence of increased sexual selectionpressure in dioecious animals, supporting the possibility thatsexual selection may play an important role in the maintenanceof sexual reproduction.     

Estimating the intensity of male-driven evolution in rodents by using X-linked and Y-linked Ube 1 genes and pseudogenes

Using sequence data from the last introns of ZFX and ZFY genes, we previously estimated the male-to-female ratio () of mutation rate to be close to 6 in higher primates and 1.8 in rodents. As the mutation rate may vary among different regions of the mammalian genome, it is interesting to see whether sequence data from other regions will give similar estimates. In this study, we have determined the partial genomic sequences of the ubiquitin-activating enzyme El genes (Ube 1x and Ube 1y for the X-linked and Y-linked homologues, respectively) of mice and rats and two mouse Ube 1y pseudogenes. From the intron sequences of the Ube 1 genes, we calculated the divergence of the Y-linked genes (Y = 0.161) and that of the X-linked genes (X = 0.107) between mouse and rat, and found the Y/X ratio to be 1.50. This ratio led to an estimate of = 2.0 with a 95% confidence interval of (1.0, 3.9). Similar estimates of were obtained if mouse Ube 1y pseudogenes were used instead of the mouse Ube 1y functional gene. These estimates are consistent with our previous estimate for rodents and suggest that the sex ratio of mutation rate in rodents is approximately only one-third of that in higher primates. Our estimate of the divergence time between Ube 1x and Ube 1y supports the view that the two genes separated before the eutherian radiation.Correspondence to: W.-H. Li     

Characterizing the time dependency of human mitochondrial DNA mutation rate estimates

Previous research has established a discrepancy of nearly anorder of magnitude between pedigree-based and phylogeny-based(human vs. chimpanzee) estimates of the mitochondrial DNA (mtDNA)control region mutation rate. We characterize the time dependencyof the human mitochondrial hypervariable region one mutationrate by generating 14 new phylogeny-based mutation rate estimatesusing within-human comparisons and archaeological dates. Rateestimates based on population events between 15,000 and 50,000years ago are at least 2-fold lower than pedigree-based estimates.These within-human estimates are also higher than estimatesgenerated from phylogeny-based human–chimpanzee comparisons.Our new estimates establish a rapid decay in evolutionary mutationrate between approximately 2,500 and 50,000 years ago and aslow decay from 50,000 to 6 Ma. We then extend this analysisto the mtDNA-coding region. Our within-human coding region mutationrate estimates display a similar, though less rapid, time-dependentdecay. We explore the possibility that multiple hits explainthe discrepancy between pedigree-based and phylogeny-based mutationrates. We conclude that whereas nucleotide substitution modelsincorporating multiple hits do provide a possible explanationfor the discrepancy between pedigree-based and human–chimpanzeemutation rate estimates, they do not explain the rapid declineof within-human rate estimates. We propose that demographicprocesses such as serial bottlenecks prior to the Holocene couldexplain the difference between rates estimated before and after15,000 years ago. Our findings suggest that human mtDNA estimatesof dates of population and phylogenetic events should be adjustedin light of this time dependency of the mutation rate estimates.     

Microevolutionary selection dynamics acting on immune genes of the green‐veined white butterfly,Pieris napi

Insects rely on their innate immune system to successfully mediate complex interactions with their microbiota, as well as the microbes present in the environment. Previous work has shown that components of the canonical immune gene repertoire evolve rapidly and have evolutionary characteristics originating from interactions with fast‐evolving microorganisms. Although these interactions are likely to vary among populations, there is a poor understanding of the microevolutionary dynamics of immune genes, especially in non‐Dipteran insects. Here, we use the full set of canonical insect immune genes to investigate microevolutionary dynamics acting on these genes between and among populations by comparing three allopatric populations of the green‐veined white butterfly, Pieris napi (Linné; Lepidoptera, Pieridae). Immune genes showed increased genetic diversity compared to genes from the rest of the genome and various functional categories exhibited different types of signatures of selection, at different evolutionary scales, presenting a complex pattern of selection dynamics. Signatures of balancing selection were identified in 10 genes, and 17 genes appear to be under positive selection. Genes involved with the cellular arm of the immune response as well as the Toll pathway appear to be enriched among our outlier loci, regardless of functional category. This suggests that the targets of selection might focus upon an entire pathway, rather than functional subsets across pathways. Our microevolutionary results are similar to previously observed macroevolutionary patterns from diverse taxa, suggesting that either the immune system is robust to dramatic differences in life history and microbial communities, or that diverse microbes exert similar selection pressures.